There is currently great commercial interest in developing micro- and nano-scale biosensors for point of care diagnostics, lab-on-a-chip devices, and a variety of miniaturized sensors, including those designed to detect biological warfare agents. Virtually all of these applications require integrated sample preparation. Three processes are typically necessary for sample preparation: 1) filtering out debris that can clog micro-fluidic channels within devices and hinder the sensitivity of detection; 2) concentrating the target analyte to enhance sensitivity; and 3) releasing the target for down-stream detection at a predictable position. There is currently no existing technology to accomplish these sample preparation processes in a chip-scale device. Conventional filters and sample concentrators are impractical because they are constructed of membrane-like materials that require large pressure gradients to force a sample through their small effective diameters open to fluid flow. Standard sample preparation filters are typically nitrocellulose membranes that have about a 0.2 micron nominal pore size. The combined cross-sectional area of the pores in one of these filters is typically only about 0.3% of the total cross-sectional area of the filter. This means that the effective diameter of the flow channel in which the filter is present is greatly reduced by the presence of the filter. The pressure required to force a sample through a flow channel is inversely proportional to the fourth power of the flow channel diameter. Thus, this reduction in effective flow channel diameter can translate into a large pressure drop and resulting upstream pressure requirement that cannot currently be incorporated into a chip-scale device. Large pressure drops, which are easily generated on bench-top instruments, such a micro centrifuges, cannot be easily generated within micro-devices. Currently, macro-scale, off-line pumps separate from the micro-device are typically required to pass sample fluids through filters in micro-scale biosensors or other micro-scale devices.
Another impediment to integrating standard sample preparation components into chip-scale sensors is reusability. Currently available filters are typically single-use, non-reusable components, which, if integrated into chip-scale biosensors, would render these expensive devices single-use and non-reusable. Additionally, integration of such components would require the use of connectors, which in the micro-scale, have been plagued with leakage and rupture problems.